This application describes one of five proposals being submitted in conjunction with the network application entitled, "The Menopausal Symptoms Initiative -Finding Lasting Answers to Sweats and Hot Flashes (MSI- FLASH)". Our network and data coordinating center (DCC) will be jointly led by two Co-PIs of the Women's Health Initiative, Clinical Coordinating Center (Seattle) who have worked together for over a decade (LaCroix, Anderson, PIs). The MSI-FLASH network has five clinical sites: Boston, MA (Cohen, Joffe, PIs); Indianapolis, IN (Carpenter, PI); Oakland, CA (Sternfeld, Caan, PIs); Philadelphia, PA (Freeman, PI); and Seattle, WA (Newton, Reed, PIs). This multidisciplinary investigator group proposes five randomized controlled trials testing a range of behavioral, mind-body, hormonal and pharmacologic interventions. Our overall goal is to fulfill the main objective of the RFA, "New Interventions for Menopausal Symptoms (U01)", to accelerate the identification of effective remedies for vasomotor symptoms (VMS). In this site application we propose a multicenter, factorial design, RCT of yoga, ultra low-dose estradiol (E2) gel and placebo gel to be conducted in Seattle, Indianapolis and Boston. The primary aims are to: 1. Evaluate the effects of yoga vs. no yoga on: a) subjective VMS frequency; and b) VMS bothersomeness; and 2. Evaluate the effects of ultra-low dose estrogen (E2) gel vs. placebo gel on: a) subjective VMS frequency; and b) bothersomeness. Our hypotheses are that 1. The effect of yoga will be greater than no yoga on: a) subjective VMS frequency and b) VMS bothersomeness; and 2. The effect of ultra-low dose E2 gel will be greater than no E2 gel on: a) subjective VMS frequency; and b) bothersomeness. Our secondary aims are: 1. To evaluate the effects of yoga and ultra-low dose E2 gel on other common menopause outcomes including: a) objective VMS frequency (Bahr monitor); b) sleep (PSQI, Actigraph"); and c) mood (CESD, HADS); and 2. To examine whether the combined effect of yoga and ultra low-dose E2 on our primary and secondary outcomes is greater than the effect of either alone. To accomplish our specific aims we will: 1) recruit and randomize 400 women to one of 4 treatment arms for 12 weeks (placebo gel; yoga + placebo gel; ultra low-dose E2 gel; yoga + ultra low-dose E2 gel); 2) measure primary and secondary outcomes at baseline and 12 weeks; and 3) compare changes in outcomes in yoga and ultra low-dose E2 gel groups to placebo; and 4) compare changes in primary and secondary outcomes for yoga + ultra low-dose E2 gel to the effects of either intervention alone (if yoga alone is efficacious). [unreadable] [unreadable] [unreadable]